Although intervertebral disc degeneration is a leading cause of musculoskeletal disability leading to pain, work loss and high cost to industry, a clear understanding of mechanisms of disease pathogenesis and specific therapeutic approaches is still lacking. Few studies have been directed toward parallel and sequential assessment of biochemical, biomechanical and anatomic responses. The proposed investigations in a well-defined model are designed to utilize biochemical, biomechanical, histopathologic and histomorphometric methods to define the pathophysiologic processes taking place during intervertebral disc degeneration. The specific objectives of the studies are designed to 1) determine whether biochemical and physicochemical changes in the intervertebral disc and vertebral bodies precede or follow alterations in joint biomechanics and structure. Correlative studies will utilize measurements of disc hydration and swelling pressure responses to assess physicochemical changes; and fixed charge density (FCD) measurements to assess proteoglycan alterations. Biomechanical assessment of disc alterations will be evaluated utilizing measurements of disc responses in bending and compression modes. 2) determine whether subchondral bone responses precede and initiate/contribute to alterations in the intervertebral disc. This question will be investigated utilizing both sequential fluorochrome labeling, and quantitative measurements of subchondral bone responses utilizing an automated image analysis system (Bioquant IV). 3) determine whether alterations in collagen cross-linking and/or non-enzymatic glycosylation play a major role in the disc degenerative process. In addition to assessing de novo responses of these biochemical parameters, the effect of variations in biomechanical stresses on the rate and degree of these responses will be investigated.